Major stem cell study debunked on scientific social network

ResearchGate has
found itself at the centre of an international debunking of a
Japanese paper that claimed to have found a simple way to generate
pluripotent stem cells.

The social network for scientists launched in 2008 as a push
back against traditional academia and the peer review process. It
has now launched Open Review as part of that platform, a system that lets users
"publish an open and transparent review of any paper that you have
read, worked with, or cited" with the central question always being
"is this research reproducible?" Professor Kenneth Ka Ho Lee, chief
of stem cell research at the Chinese University of Hong Kong, found the answer was no.

"We even repeated it three times -- we're quite confident it
doesn't work," Lee told Wired.co.uk. "If we had only repeated it
once it would not have been fair on the author."

The papers in question were published in Nature and
experiments were carried out at the Riken Institute in Japan. It is
lead author, 30-year-old Haruko Obokata, who has been in the firing
line.

The papers describe a technique whereby adult mouse blood cells
are transformed into pluripotent stem cells after being submerged
in an acid bath. The paper was groundbreaking and the method was
seen as having the potential to massively speed up human stem cell
research.

"When I read the paper, I said 'stop everything and just do this
experiment', because we thought it might work," Lee told
Wired.co.uk. This was partly down to the fact that Teruhiko
Wakayama, a cloning expert from the Yamanashi University, was named
as a co-author on the study. He has since called for the papers to be retracted after more and more
speculation emerged over duplicated images from old papers were
identified in the studies, along with several other irregularities
now being investigated at Riken.

"He is very reputable and was the first guy to clone a mouse,"
said Lee. "So when the paper came out I half believed the process.
When we first started I thought 'great, we could be the first to
try the experiment in human cells. If we could produce it in human
cells we can get published'."

As soon as the papers were out, around two months ago, Lee got
half his postdoctoral students on the case. "Everyone got involved.
It was good experience and quite a good example of what you can do
when everyone comes together."

The technique failed in human cells, so Lee and his team went
back to the mouse cells. "That didn't work and then Obokata
produced a new protocol because so many people were trying it and
there was lots and lots of noise. We were quite fast on that
because when it came out we already had the mice in place, the
culture mediums and the team had experience because we'd been
working on human cells."

With the new protocol intact, the method still failed
repeatedly.

"I feel sympathy for that girl," said Lee. "I don't know why she
did it. People who work in labs for years appear not to get
anywhere and they get frustrated."

He does, however, speculate that it could have been a totally
honest mistake.

Research teams testing stimulus-triggered acquisition of
pluripotency cell (STAP) performance-modify those cells to light up
green in response to specific wavelengths of light. After Obokata
and her team saw that the cells turned into an embryonic state
after a few days in the acid bath, they placed them in a
genetically modified mouse embryo and as it developed, looked to
see if those cells proliferated throughout the mouse. The cells,
indeed, were shown to be green throughout the mouse's tissue and
organs.

"You start looking at the cells and they turn green -- that's
what she reported," said Lee. "I've been doing this for long time
and you get false positives. But if you're expecting the results
and see this image you might think 'wow, that's working'. I'd
believe it if I'd been trying myself. Perhaps she got to a stage
where she believed it, and once she made it she had to prove they
are pluripotent by generating an embryo -- she gave those cells to
Wakayama to stick it into the embryos."

Wakayama has since, however, admitted that when it came to those cells, "I myself don't know
what I used in my experiments". He has since handed those cells
remaining in his possession to a third-part investigation.

An investigation
carried out by the Riken Institute in Japan has so far
concluded that although "there had been inappropriate handling of
data for two of the items under investigation", it did not amount
to misconduct and there was "no malice intended". It will continue
investigating four other claims of misconduct, and will attempt to
reproduce the cells as well. Lee has simply beaten them to it, and
published those results on Open Review.

"It's a platform that can be used to quickly refute something
that doesn't work," Lee told Wired.co.uk. "You don't have to say it
blatantly. You might say 'this molecule probably shouldn't be
added'. Because if we challenge someone and say they're wrong, if
then your paper falls into their lap they will kill it."

Lee paints a picture of traditional peer-review as riddled with
jealousies and deception, and in a massive need of a reboot. It's
something ResearchGate founder Ijad Madisch knew when he launched
the platform. "It's not the first time poor-quality research has
been taken as scientific fact," he says on the website. "All too
often we've seen false findings printed in the pages of noteworthy
journals, and rarely is anything done about it. Because of where
they were published these findings go on to form the basis of
further work, and solid research becomes lost in this noise. This
is a clear sign that the way research is currently evaluated and
published is broken. Peer review isn't working.

"Science must be open. This is why we're launching Open Review,
a feature that approaches the evaluation of research in a different
way, an open way."

"Peer review is a major problem," says Lee. "I have problems
with people delaying me for eight months, then suddenly they
produce the same charts. They hold you up because they have similar
results and want to publish ahead of you -- there are dirty little
tricks in academia."

It's why we have seen the rise of academic fraud, as detailed in a recent report by
Science author Mara Hvistendahl. She uncovered
publicly advertised toll-free hotlines in China that help you
buy citations or whole papers, ready to be submitted to prestigious
academic journals for publication.

Lee said he was already investigating several other papers he
believed to be inaccurate.

"I trained in Scotland, and there you say what you mean," he
said. "And this is what it means to be a scientist. Integrity."

The results of Lee's investigations can be read on Open Review, where scientists from
the National Institutes of Health, École
Polytechnique Fédérale de Lausanne and Ottawa Hospital
Research Institute are already debating the results with the
professor.